The resolution of one enantiomer from a racemic mixture is often required in pharmaceutical and other chemical industries. Such resolution is generally conducted by selectively acylating the desired enantiomer with an acylating agent in the presence of an enzyme catalyst while the other enantiomer is simultaneously racemized in situ by the action of a metal catalyst. In such a process, ruthenium complexes such as [(p-cymene)RuCl2]2 and (η5-Ph4C4CO)2H(μ-H)(CO)4Ru2 (Shvo catalyst) have been conventionally used as a racemization catalyst, and an aryl acetate, as an acylating agent in the presence of a lipase catalyst.
However, the ruthenium cymene complex catalyzes the racemization very slowly at room temperature, and the Shvo catalyst which exists in the form of a dimer must be activated at a high temperature and it also requires the use of a hydrogen-transfer agent, e.g., the corresponding ketone to the alcohol in case a chiral alcohol is to be racemized (Y. Shvo et al, Organometallics, 8, 162, 1989).
Further, the aryl acetate used in the prior resolution method as an acylating agent generates an aryl alcohol as a by-product which is difficult to separate from the reaction product (see M. J. Kim et al, Organic Letters 2, 2377 (2000)). The use of an alkenyl acetate in place of an aryl acetate has also been attempted, but in its presence, oxidation of the target chiral alcohol occurs to some extent in the presence of the above-mentioned metal catalysts.